The development of synthetic methods for the purpose of total synthesis of natural products, especially those having physiological activity, has been a major focus for organic chemists over the past thirty years. The molecular complexity and functional group sensitivity of many of these compounds requires the availability of highly specific synthesis. We wish to extend our current research on the synthesis of antibiotic LL-Z1220 (1) to include other compounds of nature possessing similar functionality and biological activities; especially crispatone (2), tridachione (3), 9, 10-deoxytridachione (4), photodeoxytridachione (5), crispatene (6), and bissetone (7). Our efforts would later be extended to include other pyranone natural products such as podopyrene (8) and other members of the crispatone/tridachione family (9-11). One means of potential general utility for the attainment of these synthetic goals is outlined in the schemes of this proposal. This plan incorporates key synthetic methods for gamma-pyranone ring construction developed independently by Ganem and Koreeda) and the newly discovered ester enolate "mono-Claisen" rearrangement which allows for stereo-specific attachment of carbon side chains to the C-1 position of saturated pyranoid rings. Thus our proposed research would essentially have two major goals; (1) development of synthetic methodologies the total synthesis of several natural products having a wide range of biological activities, and (2) provide sufficient quantities of these compounds for further testing by the NIH. Further, a total synthesis of these systems would serve to evaluate this proposed synthetic approach. The objectives of this proposal are to describe experimental designs for the attainment of these goals.